What is considered a high dose of phenylephrine (PE)

From the Guidelines

Phenylephrine 2 mg is considered a high dose for intravenous administration, exceeding standard dosing recommendations and potentially causing significant cardiovascular effects. The typical intravenous dose of phenylephrine ranges from 0.1 mg to 0.5 mg, with a maximum single dose usually not exceeding 1 mg, as seen in the guidelines for post-cardiac arrest care 1. A 2 mg dose could potentially cause severe hypertension, reflex bradycardia, and peripheral vasoconstriction. This high dose may be used in specific emergency situations such as severe hypotension or shock under close medical supervision with continuous monitoring of blood pressure and heart rate. Some key points to consider when using phenylephrine include:

• The medication works as an alpha-1 adrenergic receptor agonist, causing vasoconstriction and increasing blood pressure 1.
• The potency of this medication means that even small increases in dosage can lead to substantial changes in blood pressure, which is why 2 mg would be considered a high dose requiring careful titration and monitoring if used clinically.
• Phenylephrine is not recommended in the treatment of septic shock except in circumstances where norepinephrine is associated with serious arrhythmias, cardiac output is known to be high and blood pressure persistently low, or as salvage therapy when combined inotrope/vasopressor drugs and low-dose vasopressin have failed to achieve MAP target 1. It's essential to note that the use of high-dose phenylephrine should be approached with caution, considering the potential risks and benefits, and should only be used under close medical supervision.

From the FDA Drug Label

10 OVERDOSAGE Overdose of phenylephrine hydrochloride can cause a rapid rise in blood pressure.

The FDA drug label does not answer the question.

From the Research

Definition of High-Dose Phenylnephrine

The definition of a high dose of phenylephrine can vary depending on the context and the patient's condition.

• In the study 2, high-dose phenylephrine was used to treat delayed ischemic deficits after subarachnoid hemorrhage, but the exact dose was not specified.
• In the study 3, phenylephrine boluses of 0.5,1.0,2.0, and 4.0 μg/kg were given to pigs, and the effects on cardiac output and venous return were measured.
• In the study 4, phenylephrine 100 mcg in 10 mL intravenously was used to treat predelivery hypotension following spinal anesthesia for cesarean section.
• In the study 5, phenylephrine was infused to raise the systolic blood pressure by 30% and 50% above baseline values in patients with chronic pulmonary hypertension, but the exact dose was not specified.

Factors Influencing the Definition of High-Dose Phenylnephrine

The definition of a high dose of phenylephrine can be influenced by several factors, including:

• The patient's condition and medical history 2, 5
• The context in which the phenylephrine is being used (e.g. treating hypotension during surgery or in patients with chronic pulmonary hypertension) 3, 4
• The dose and administration method of the phenylephrine 3, 4

Comparison of Studies

A comparison of the studies shows that the definition of a high dose of phenylephrine can vary widely depending on the context and patient population.

• The study 2 suggests that high-dose phenylephrine can be safely used in patients with delayed ischemic deficits after subarachnoid hemorrhage, even in those with preexisting cardiac disease.
• The study 3 shows that the effects of phenylephrine on cardiac output and venous return depend on the position of the heart on the Frank-Starling relationship.
• The study 4 compares the effects of a phenylephrine/ephedrine protocol versus an ephedrine-only protocol for treating predelivery hypotension following spinal anesthesia for cesarean section.
• The study 5 evaluates the effect of phenylephrine and norepinephrine in patients with chronic pulmonary hypertension.